Edited by: Banasri Hazra, Jadavpur University, India
Reviewed by: Ruchi Tiwari, U.P. Pandit Deen Dayal Upadhyaya Veterinary University, India; Andy Wai Kan Yeung, The University of Hong Kong, Hong Kong
*Correspondence: Junqing Huang,
This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Starting from December 2019, novel coronavirus disease 2019 (COVID-19) pandemic has caused tremendous economic loss and unprecedented health crisis across the globe. While the development of cure is at full speed, less attention and fewer effort have been spent on the prevention of this rapidly spreading respiratory infectious disease. Although so far, several vaccine candidates have advanced into clinical trials, limited data have been released regarding the vaccine efficacy and safety in human, not mention the long-term effectiveness of those vaccines remain as open question yet. Natural products and herbal medicines have been historically used for acute respiratory infection and generally show acceptable toxicity. The favorable stability for oral formulation and ease of scaling up manufacture make it ideal candidate for prophylactic. Hereby, we summarized the most recent advance in SARS-CoV-2 prevention including vaccine development as well as experimental prophylactics. Mainly, we reviewed the natural products showing inhibitory effect on human coronavirus, and discussed the herbal medicines lately used for COVID-19, especially focused on the herbal products already approved by regulatory agency with identifiable patent number. We demonstrated that to fill in the response gap between appropriate treatment and commercially available vaccine, repurposing natural products and herbal medicines as prophylactic will be a vigorous approach to stop or at least slow down SARS-CoV-2 transmission. In the interest of public health, this will lend health officials better control on the current pandemic.
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The novel coronavirus disease 2019 (COVID-19) pandemic starting from December 2019 has cast unprecedented threat to public health worldwide with over 27.9 million infection cases and 905,000 death till September 10, 2020, and the case number is still soaring (
SARS-CoV-2 initiate its infection
Besides vaccine development, great efforts have been dedicated to discovering effective prophylactics against COVID-19 for high risk population, whereas very limited studies give satisfactory outcome. Very recently, several clinical cases and
In this review, we aimed to provide a new perspective regarding COVID-19 prevention. We called attention to natural products and herbal medicines as potential prophylactic against COVID-19. We summarized the most recent advances in COVID-19 vaccine development and lately reported experimental prophylactics. Then, we discussed both the natural products inhibiting human coronavirus and the herbal medicines proven effective in alleviating respiratory distress syndrome. We performed integrated network analysis upon selected herbal medicine to identify the most promising active components with the potential to be prophylactics. Ultimately, this review attempts to offer alternative conceptual framework for COVID-19 prevention and deeper insight into this unprecedented pandemic.
Development of effective prevention is urged to contain the spread of current pandemic and halt the occurrence of future relapse. Vaccine, convalescent serum, monoclonal antibody, and marketed anti-viral drugs become the most promising options in the spotlight at this point. In this worldwide race to develop vaccine solution against SARS-COV-2, several candidates are standing out as the current front runners (
COVID-19 vaccines in pipeline.
Lead Developer(s) | Vaccine Type | Development Status | Ref. |
---|---|---|---|
Moderna & NIAID | mRNA/nanoparticle | Phase III clinical trials ongoing | ( |
AstraZeneca & University of Oxford | Plasmid edited gene materials/AdV | Phase I/II ongoing; phase II/III recruiting | ( |
CanSino Biologics & Academy of Military Medical Sciences | Plasmid edited gene materials/Ad5 | Phase I/II ongoing in China, phase I/II approved in Canada | ( |
Sinovac Biotech & Wuhan Institute of Biological Products | Inactivated SARS-COV-2 | Phase I/II ongoing | ( |
Inovio Pharmaceuticals | SARS-COV-2 encoding DNA based | Phase I ongoing | ( |
BioNTech & Pfizer | mRNA vaccine | Phase II/III ongoing | ( |
Novavax | Recombinant Protein | Phase I complete, phase II ongoing | ( |
Johnson & Johnson | Recombinant Protein | Phase I/II ongoing, accelerating phase III | ( |
Curevac | mRNA vaccine | Phase I ongoing | ( |
Imperial College London | RNA vaccine | Phase I/II ongoing | ( |
Russia Ministry of Health | Plasmid edited gene materials/AdV | Phase III ongoing, approved | ( |
Most potential options can be broadly categorized three types: mRNA delivery, genetic material with viral carrier, and inactivated virus. Currently, more vaccines candidates on the most advanced timeline are in the second and third category for those methods have more responsive and rapid production scheme, suitable for emergent public health crisis of SARS-COV-2.
Two leading candidates on mRNA delivery are the mRNA-1273 by Moderna in collaboration with National Institute of Allergy and Infectious Diseases (NIAID) in the U.S., and BNT162b1 by BioNTech in collaboration with Pfizer in Germany. Both candidates use RNA motifs of encoding sequence for the Spike (S) protein. Since the commence of the vaccine, Moderna has announced FDA’s permission for phase III recruitment starting July 2020, implying expedited development is currently on track to delivery optimistically by late 2020 (
Moreover, numerous contenders are collaborating with governments and philanthropic foundations to ramp up production to create stockpile once clinical trials provide evidence for their safety and efficacy, to shorten deployable timeline. NIAID also recently announce an establishment of a new clinical trial network focusing on COVID-19 vaccine and monoclonal antibody testing. However, mRNA vaccine, such as Moderna’s mRNA-1273, has yet to be approved and adopted historically. Lack of similar predecessor likely warrants more scrutiny from regulators and general publics.
Convalescent serum transfusion, where patient received recovered patients’ antibodies-contained plasma to develop the ability to fight viral infection, is currently widely trialed as treatment option for COVID-19 around the world. In April 2020, National Health Service (NHS) in the UK has established Blood and Transplant Service (NHSBT) to conduct recovery trial with Oxford University, studying the application viability of such technology on COVID treatment as well as prevention (
More recently, monoclonal antibody discovery against SARS-CoV-2 has yield valuable insight into variation of viable antibodies and their mechanisms. Wu et al. discussed the wide variation in neutralizing antibody (NAb) potency among infected patients, which was indicated with NAb titer (ID50: 200 ~ 21567) ranging across two orders of magnitudes (
Remdesivir, developed by Gilead Sciences, acts as a prodrug of a nucleotide analog. When it is intracellularly metabolized, its product, analogue of adenosine triphosphate, will inhibit regular viral RNA polymerase’s function. It is considered applicable in board spectrum to multiple other coronaviruses, such as Ebola, MERS-COV, and SARS-COV. Remdesivir is not only propelled as a treatment against SARS-COV-2, but also is under investigation for prevention purpose. Early experiment of remdesivir by
Emtricitabine/tenofovir disoproxil, also commonly known for its brand name TRUVADA® in the U.S., an HIV pre-exposure prophylactic. It is a combination of protease inhibitor and nucleotides reverse transcriptase inhibitor. It is considered to have beneficial effect on treating SARS-COV-2 with its possible inhibition of RNA-dependent RNA polymerase. A recent cohort study also suggests that AIDS patient taking antiretroviral therapy, especially tenofovir disoproxil fumarate/emtricitabine has lower risks of diagnosis, and reduced severity and fatality (
Lopinavir/ritonavir, brand name KALETRA® in the U.S., is a combination used as an HIV aspartate protease inhibitor previously, has
Although combinatorial synthesis coupled with molecular docking help discover numerous synthetic drugs, more than one third of Food and Drug Administration (FDA)-approved drugs are natural products (
Natural products inhibiting human coronavirus.
Natural products potentially effective for COVID-19.
Natural Product | Inhibited Virus | Drug Targets/Relevant Signaling | Mechanism of Action | Ref. |
---|---|---|---|---|
Dihydrotanshinone |
MERS-CoV |
S protein of MERS-CoV |
Block MERS-CoV entry using pre-and post-attachment assay |
( |
Ouabain |
MERS-CoV |
S protein of MERS-CoV |
Block MERS-CoV entry by HCS assay, IC50 in Vero cells: 0.08 µM |
( |
Griffithsin |
MERS-CoV |
S protein of MERS-CoV |
Inhibit spike protein function during entry |
( |
Silvestrol |
MERS-CoV |
eIF4A |
Inhibit eIF4A, EC50: 1.3 nM |
( |
Emodin |
SARS-CoV |
S protein and ACE2 interaction |
Blocked the binding of S protein to ACE2 using biotinylated ELISA assay, IC50: 200 μM |
( |
Scutellarein |
SARS-CoV |
SARS-CoV helicase protein |
Inhibit the nsP13ATPase activity by FRET-based double-strand (ds) DNA unwinding assay, IC50: 0.86 ± 0.48 μM |
( |
Tannic acid |
SARS-CoV |
3CLPro |
Inhibition of 3CLPro, IC50: 3 µM |
( |
Theaflavin-3-gallate |
SARS-CoV |
3CLPro |
Blocking 3CLPro function, IC50: 7 µM |
( |
Escins |
SARS-CoV |
NF‐κB and activator protein-1 signaling pathways |
Decrease levels of TNF‐α and IL‐6, EC50: 1.5 and 2.4 μg/ml in HCLE and NHC cells |
( |
Daidzin |
SARS-CoV-2 |
HSPA5 |
High binding affinity to HSPA5 SBDβ tested by virtual docking |
( |
Genistein | ||||
Formononetin | ||||
Biochanin A | ||||
Lead compounds from |
SARS-CoV-2 |
PL protein |
High binding affinity to PLpro tested by molecular docking |
( |
10-Hydroxyusambarensine | SARS-CoV-2 | 3CL protein | High binding affinity to 3CLpro tested by tested by molecular docking | ( |
6-Oxoisoiguesterin |
||||
22-Hydroxyhopan-3-one | ||||
Gallic acid |
SARS-CoV-2 |
RdRp |
High binding affinity to RdRp tested by molecular docking |
( |
Quercetin |
||||
Withanone |
SARS-CoV-2 |
TMPRSS2 |
Bind and interact at the catalytic site of TMPRSS2 |
( |
MERS-CoV causes Middle East respiratory syndrome (MERS, also known as camel flu). It was first discovered in 2012 in Saudi Arabia. Since then, it has spread to 27 countries through air travel of infected people (
The envelope spike (S) protein of MERS-CoV is important for dipeptidyl peptidase 4 receptor binding and virus-cell membrane fusion, thus it is the key for virus to entry host cells (
Ouabain is from the seeds of
Griffithsin isolated from the
Besides inhibiting MERS-CoV entry host cells, suppressing its replication is an alternative strategy. Silvestrol, a natural compound isolated from the plant
From 2002 to 2003, SARS-CoV emerged in Southern China, infecting more than 8,000 people and causing approximately 800 fatalities mostly in China and its neighboring countries. Like MRES-CoV, the envelope S protein of SARS-CoV is also essential for virus tropism and invasion into host cells, which is a potential target for the development therapeutics (
Emodin, an anthraquinone from
Scutellarein is a flavone found in
Chymotrypsin-like protease (3CLPro) of SARS-CoV, an enzyme responsible for proteolysis, is vital to coronavirus replication, making it considered as an important target for drug discovery against SARS-CoV. Chen et al. (
The current COVID-19 pandemic caused by SARS-CoV-2 was identified in Wuhan City, in Hubei province of China. The number of infection case is still progressively growing. The genome of SARS-CoV-2 has over 70% similarity to that of SARS-CoV (
Heat Shock Protein A5 (HSPA5, also known as BiP or GRP78) is one of the host-cell receptors that have been reported to be recognized by virus S protein. When infected, HSPA5 is upregulated and translocated to the cell membrane where it is recognized by the SARS-CoV-2 spike to drive the infection process. Elfiky et al. (
The host enzyme transmembrane protease serine 2 (TMPRSS2) facilitates viral particle entry into host cells. Inhibiting of this enzyme blocks virus fusion with ACE2, making it a potential target to inhibit virus entry. By molecular docking and molecular dynamics simulations,
SARS-CoV-2 papain-like protease (PL pro) cleaves the viral polyproteins a/b which is essential for its survival and replication. Thus, PL pro is one of the prospective drug targets of SARS-CoV-2. Goswami et al. (
Besides S protein and PLpro, the other promising drug target for combating the infection of SARS-CoV-2 is 3-chymotrypsin-like protease (3CLpro, also known as main protease). The conserved 3CLpro controls virus replication.
RNA-dependent RNA polymerase (RdRp) is an essential virus replicase that catalyzes the synthesis of complementary RNA strands using the virus RNA template. The molecular structure of RdRp was revealed in May 2020 (
The researches mentioned above are all still in preliminary stages of drug development although they have shown great potentials against SARS-CoV-2 using computer-based screening. Further pre-clinical studies have to be performed to examine the anti-viral effects of those lead compounds. In the meanwhile, great number of clinical trials have registered to investigate the potentials of natural product to halt disease progression. For example, Koshak et al. from King Abdulaziz University will investigate the effects of Nigella sativa seed oil with immunomodulation and antiviral activity in hospitalized adult patients diagnosed with COVID-19 (
Herbal medicines like EPs® 7630, Sinupret®, and KanJang® have proven track record of treating acute respiratory infection due to common cold or influenza (
A clinical case went public in March 2020 showed that a herbal formulation recommended by National Health Commission of the P.R. China (NHC) was effective in attenuating acute respiratory distress syndrome in a mild COVID-19 patient (
Li et al. tested the potency of Lian-Hua-Qing-Wen, a licensed herbal formulation in inhibiting SARS-CoV-2 infection of Vero E6 cells using cytopathic effect inhibition assay and plaque reduction assay (
Based on recently emerging studies, we reviewed all the herbal products both used for COVID-19 and approved by regulatory agency of which the patent numbers are identifiable. We summarized the composition and prospective drug targets of those licensed herbal products (
Licensed Chinese herbal medicines for acute respiratory infection.
Herbal Medicines | Affected Pathways Potential Targets | Composition | Ref. | |
---|---|---|---|---|
Herbal components | Original Species | |||
Lian-Hua-Qing-Wen | MAPK8, IL-6, COX-2, sEH, RELA, cPLA2α, mPGES-1, TNF, DPP4, IL-1β, CASP3, MAPK1, EGFR, BAX, BCL2, JUN, PIK3CG. | Forsythiae Fructus |
|
( |
Lonicerae Japonicae Flos |
|
|||
Ehedraep Herba |
|
|||
Armeniacae Seman Amarum |
|
|||
Gypsum Fibrosum† | ||||
Isatidis Radix |
|
|||
Dryopteridis Crassirhizomatis Rhizoma |
|
|||
Houttuyniae Herba |
|
|||
Pogostemonis Herba |
|
|||
Rhei Radix Et Rhizoma |
|
|||
Rhodiolae Crenulatae Radix Et Rhizoma |
|
|||
Menthol |
|
|||
Glycyrrhizae Radix Et Rhizoma |
|
|||
Huo-Xiang-Zheng-Qi | PTGS2, HSP90AB1, mPGES-1, LTA4H, NOS2, PTGS2. | Atractylodis Rhizoma |
|
( |
Citri Reticulatae Pericarpium |
|
|||
Magnoliae Officinalis Cortex |
|
|||
Angelicae Dahuricae Radix |
|
|||
Poria mushroom§ |
|
|||
Arecae Pericarpium |
|
|||
Pinelliae Rhizoma |
|
|||
Glycyrrhizae Radix Et Rhizoma |
|
|||
Pogostemonis Herba |
|
|||
Perillae Folium |
|
|||
Jin-Hua-Qing-Gan | COX-2, sEH, 5-LOX, PTGS2, AKTI, HSP90AA1, RELA, MAPK1, CASP3, TP53, ALB, TNF, IL6, MAPK8, MAPK14. | Lonicerae Japonicae Flos |
|
( |
Gypsum Fibrosum† | ||||
Ehedraep Herba |
|
|||
Armeniacae Seman Amarum |
|
|||
Scutellariae Radix |
|
|||
Forsythiae Fructus |
|
|||
Fritillaria Thunbergii Bulbus |
|
|||
Anemarrhenae Rhizoma |
|
|||
Arctii Fructus |
|
|||
Artemisiae Annuae Herba |
|
|||
Menthae Haplocalycis Herba |
|
|||
Glycyrrhizae Radix Et Rhizoma |
|
|||
Shu-Feng-Jie-Du | IL6, IL1B, CCL2, IL2, MAPK8, MAPK1, MAPK14, CASP3, FOS, ALB, IL4, IL1B, EGFR, FOS, AR, BCL2L, NOS2, F10, PTGS2, PTGS1, ESR1, DPP4. | Polygoni Cuspidati Rhizoma |
|
( |
Forsythiae Fructus |
|
|||
Isatidis Radix |
|
|||
Bupleuri Radix |
|
|||
Patriniae Herba |
|
|||
Vervain |
|
|||
Phragmitis Rhizoma |
|
|||
Glycyrrhizae Radix Et Rhizoma |
|
|||
Su-He-Xiang | N/A | Styrax |
|
( |
Benzoinum |
|
|||
Borneolum Syntheticumc |
|
|||
Bubali Cornu* |
|
|||
Moschus* |
|
|||
Santali Albi Lignum |
|
|||
Aquilariae Lignum Resinatum |
|
|||
Aucklandiae Radix |
|
|||
Cyperi Rhizoma |
|
|||
Olibanum |
|
|||
Long Pepper Fruit. |
|
|||
Atractylodis Macrocephalae Rhizoma |
|
|||
Chebulae Fructus |
|
|||
Cinnabaris† | ||||
An-Gong-Niu-Huang | N/A | Bovis Calculus* |
|
( |
Bubali Cornu* |
|
|||
Moschus* |
|
|||
Margarita* | ||||
Cinnabaris† | ||||
Arsenic (II) sulfide† | ||||
Coptidis Rhizoma |
|
|||
Scutellariae Radix |
|
|||
Gardeniae Fructus |
|
|||
Curcumae Radix |
|
|||
Borneolum Syntheticumc |
|
|||
Xi-Yan-Ping | N/A | Andrographolide sulfonatesc |
|
( |
Xue-Bi-Jing | LTA4H, 12-LOX, IL2, cPLA2, IL6, RELA, TNF, PTGS2, IL10, NOS2α, CASP3, MAPK1. | Carthami Flos |
|
|
Paeoniae Radix Rubra |
|
|||
Chuanxiong Rhizoma |
|
|||
Salvia miltiorrhiza Radix Et Rhizoma |
|
|||
Angelicae Sinensis Radix |
|
|||
Re-Du-Ning | COX-2, sEH, IL6, CCL2, CASP3, IL4, MAPK1, RELA, FOS, NOS2, IL1B, CXCL10, MAPK14, EGFR. | Artemisiae Annuae Herba |
|
( |
Lonicerae Japonicae Flos |
|
|||
Gardeniae Fructus |
|
|||
Tan-Re-Qing | COX-2, sEH, LTA4H, IL6, IL1B, IL10, MAPK1, IL4, CXCL8, MAPK14, EGFR, CXCL10. | Scutellariae Radix |
|
( |
Saigae Tataricae Cornu* |
|
|||
Lonicerae Japonicae Flos |
|
|||
Forsythiae Fructus |
|
|||
Xing-Nao-Jing | N/A | Moschus* |
|
|
Borneolum Syntheticum |
|
( |
||
Gardeniae Fructus |
|
|||
Curcumae Radix |
|
|||
Shen-Fu | N/A | Ginseng Radix Et Rhizoma |
|
( |
Aconiti Lateralis Radix Praeparata |
|
|||
Sheng-Mai | IL6, GAPDH, ALB, TNF, MAPK1, MAPK3, TP53, EGFR, CASP3. | Ginseng Radix Et Rhizoma |
|
( |
Ophiopogonis Radix |
|
|||
Pu-Di-Lan | N/A | Scutellariae Radix |
|
( |
Traxaci Herba |
|
|||
Corydalis bungeana |
|
|||
Isatidis Radix |
|
|||
Yin-Qiao | N/A | Forsythiae Fructus |
|
( |
Lonicerae Japonicae Flos |
|
|||
Platycodonis Radix |
|
|||
Menthae Haplocalycis Herba |
|
|||
Phyllostachydis Henonis Folium |
|
|||
Glycyrrhizae Radix Et Rhizoma |
|
|||
Schizonepetae Herba |
|
|||
Sojae Semen Praeparatum |
|
|||
Arctii Fructus |
|
|||
Yu-Ping-Feng-San | N/A | Saposhnikoviae Radix |
|
( |
Astragali Radix |
|
|||
Atractylodis Macrocephalae Rhizoma |
|
|||
Sang-Ju | N/A | Mori Folium |
|
( |
Chrysanthemi Flos |
|
|||
Almond |
|
|||
Forsythiae Fructus |
|
|||
Menthae Haplocalycis Herba |
|
|||
Platycodonis Radix |
|
|||
Glycyrrhizae Radix Et Rhizoma |
|
|||
Phragmitis Rhizoma |
|
|||
Shuang-Huang-Lian | N/A | Lonicerae Japonicae Flos |
|
( |
Scutellariae Radix |
|
|||
Forsythiae Fructus |
|
|||
Ma-Xing-Shi-Gan | N/A | Ehedraep Herba |
|
( |
Almond |
|
|||
Glycyrrhizae Radix Et Rhizoma |
|
|||
Gypsum Fibrosum† | ||||
Bai-He-Gu-Jin | N/A | Rehmanniae Radix |
|
( |
Angelicae Sinensis Radix |
|
|||
Paeoniae Radix Alba |
|
|||
Glycyrrhizae Radix Et Rhizoma |
|
|||
Platycodonis Radix |
|
|||
Scrophulariae Radix |
|
|||
Fritillaria Thunbergii Bulbus |
|
|||
Ophiopogonis Radix |
|
|||
Lilii Bulbus |
|
|||
Ren-Shen-Bai-Du | N/A | Chinese Thorawax Root. |
|
( |
Glycyrrhizae Radix Et Rhizoma |
|
|||
Incised Notopterygium Rhizome Root |
|
|||
Doubleteeth Angelicae Root |
|
|||
Chinese Thorawax Root |
|
|||
Common Hogfennel Root |
|
|||
Chuanxiong Rhizoma |
|
|||
Submature Bitter Orange |
|
|||
Menthae Haplocalycis Herba |
|
|||
Poria mushroom§ |
|
|||
Platycodonis Radix |
|
|||
Glycyrrhizae Radix Et Rhizoma |
|
|||
Ginger |
|
†Mineral products; §Fungus-derived products; *Animal-derived products; Components without labelling are all plant-derived products.
Chinese herbal medicines alleviating acute respiratory infection
Lead compounds with greatest drug-likeness isolated from herbs for COVID-19.
Since early 2020, numerous pharma companies collaborating with academics or state-sponsored research institute have joined the race of therapy development to combat wildly spreading COVID-19. As of July 2020, a range of various therapeutics has been discovered, from small molecules, neutralizing antibodies, to bioengineered products. Aided with computational chemistry and virtual screening, researchers has established a large library of novel small molecules, showing favorable binding affinity with validated drug targets (
Since the outcome of current therapeutics in severe/critical COVID-19 patients are still debatable, prevention rather than treatment becomes more important to restrain this pandemic. Blocking the entry of SARS-CoV-2 and suppressing infection at initial stage are considered as more practical strategy (
Pros and cons of current prevention of COVID-19 (Created with BioRender.com).
Natural products and herbal medicine have long track record to treat respiratory infection and many have been approved as drugs, over-the-counter nutrition or food additives. Those products generally have satisfactory safety profiles. The minimal toxicity makes natural product and herbal medicines ideal prophylactic candidates for long-term use. Based on recent
Conceptualization: GT, JC, and JH. Writing—original draft preparation: GT, JL, and JC. Writing—review and editing: GT, JL, JC, and JH. Visualization: ZH, JH. Supervision: GT and JH. Funding acquisition: J-xC and JH. All authors contributed to the article and approved the submitted version.
This work is supported by the Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University (No. 201911).
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
We greatly appreciate the comments from Michael Heinrich, University College London (UCL) School of Pharmacy for manuscript preparation.
ACE2, angiotensin-converting enzyme 2; ADMET, absorption, distribution, metabolism, excretion and toxicity; AKTI, Akt inhibitor; ALB, albumin; AR, androgen receptor; BAX, Bcl-2 Assaciated X protein; BCL2, B-cell lymphoma-2; BCL2L, bcl2-like gene; CASP3, caspases-3; CCL2, chemokine (C-C motif) ligand 2; COX-2, cyclooxygenase-2; COVID-19, coronavirus disease 2019; CoVs, coronaviruses; cPLA2, cytosolic Phospholipase A2; cPLA2α, cytosolic Phospholipase A2α; CXCL10, CXC motif chemokine 10; CXCL8, CXC motif chemokine 8; DPP4, Dipeptidyl peptidase-4; EGFR, Epidermal Growth Factor Receptor; ESR1, Estrogen Receptor 1; F10, Coagulation Factor X; FDA, food and drug administration; FRET, fluorescence resonance energy transfer; HCoV-229E, human coronavirus 229E; FOS, Fos proto-oncogene; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HCoV-HKU1, human coronavirus HKU1; HCoV-NL63, human coronavirus NL63; HCoV-OC43, human coronavirus OC43; HCS, high-content screening; HSPA5, heat shock protein A5; HSP90AA1, heat shock protein 90 kDa alpha, class A member 1; HSP90AB1, heat shock protein 90 kDa alpha, class B member 1; IL10, interleukin 10; IL-1β, interleukin 1β; IL2, interleukin 2; IL4, interleukin 4; IL6, interleukin 6; JUN, Jun proto-oncogene; LTA4H, leukotriene A4 hydrolase; MAPK1, mitogen-activated protein kinase 1; MAPK14, mitogen-activated protein kinase 14; MAPK3, mitogen-activated protein kinase 3; MAPK8, mitogen-activated protein kinase 8; MERS-CoV, middle east respiratory syndrome-related coronavirus; mPGES-1, Microsomal prostaglandin E synthase-1; NAb, neutralizing antibody; NOS2, Nitric oxide synthase 2; NOS2α, Nitric oxide synthase 2α; NHC, national health commission of the P.R. China; NHS, national health service; NHSBT, blood and transplant service; NIAID, national institute of allergy and infectious diseases; NTP, nucleotide triphosphate; PIK3CG, Phosphatidylinositol-4; PTGS1, Prostaglandin-Endoperoxide Synthase 1; PTGS2, Prostaglandin-Endoperoxide Synthase 2; PLpro, papain-like protease; RBD, receptor-binding domain; RdRp, RNA-dependent RNA polymerase; RELA, RELA proto-oncogene; S protein, Spike protein; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SBDβ, substrate-binding domain β; sEH, soluble epoxide hydrolase; TMPRSS2, transmembrane protease; TNF, Tumor necrosis factor; TP53, tumor protein p53; WHO, world health organization; 3CLpro, 3-chymotrypsin-like protease; 5-LOX, 5-liopoxygenase; 12-LOX, 12-liopoxygenase.